pHLIP Peptide Interaction with a Membrane Monitored by SAXS

The pH (Low) Insertion Peptides (pHLIP® peptides) find application in studies of membrane-associated folding, since spontaneous insertion of these peptides is conveniently triggered by varying pH. Here we employed small angle X-ray scattering (SAXS) to investigate WT pHLIP® peptide oligomeric state in solution at high concentrations and monitor changes in liposome structure upon peptide insertion into the bilayer. We established that even at high concentrations (up to 300 μM) WT pHLIP® peptide at pH 8.0 does not form oligomers higher than tetramers (which exhibit concentration-dependent transfer to monomeric state as it was shown previously). This finding has significance for medical applications, when high concentration of the peptide is injected into blood and diluted in blood circulation. The interaction of WT pHLIP® peptide with liposomes does not alter the unilamellar vesicle structure upon peptide adsorption by lipid bilayer at high pH or upon insertion across the bilayer at low pH. At the same time, SAXS data clearly reflect the insertion of the peptide into the membrane at low pH, which opens the possibility to investigate kinetic process of a polypeptide insertion and exit from the membrane in real time by time-resolved SAXS

BRST approach to Lagrangian formulation for mixed-symmetry fermionic higher-spin fields

We construct a Lagrangian description of irreducible half-integer higher-spin representations of the Poincare group with the corresponding Young tableaux having two rows, on a basis of the BRST approach. Starting with a description of fermionic higher-spin fields in a flat space of any dimension in terms of an auxiliary Fock space, we realize a conversion of the initial operator constraint system (constructed with respect to the relations extracting irreducible Poincare-group representations) into a first-class constraint system. For this purpose, we find auxiliary representations of the constraint subsuperalgebra containing the subsystem of second-class constraints in terms of Verma modules. We propose a universal procedure of constructing gauge-invariant Lagrangians with reducible gauge symmetries describing the dynamics of both massless and massive fermionic fields of any spin. No off-shell constraints for the fields and gauge parameters are used from the very beginning. It is shown that the space of BRST cohomologies with a vanishing ghost number is determined only by the constraints corresponding to an irreducible Poincare-group representation. To illustrate the general construction, we obtain a Lagrangian description of fermionic fields with generalized spin (3/2,1/2) and (3/2,3/2) on a flat background containing the complete set of auxiliary fields and gauge symmetries.Comment: 41 pages, no figures, corrected typos, updated introduction, sections 5, 7.1, 7.2 with examples, conclusion with all basic results unchanged, corrected formulae (3.27), (7.138), (7.140), added dimensional reduction part with formulae (5.34)-(5.48), (7.8)-(7.10), (7.131)-(7.136), (7.143)-(7.164), added Refs. 52, 53, 54, examples for massive fields developed by 2 way

GENERATION OF ELECTRON BEAMS IN MAGNETRON GUNS WITH SECONDARY EMISSION CATHODES OF A SMALL DIAMETER

This paper is concerned with investigations on electron beam generation in magnetron guns with cold secondary-emission metallic cathodes of a small diameter with a large aspect ratio. The parameters of electron beams are given as a function of electric and magnetic field values using different methods of voltage pulse formation for secondary-electron multiplication and beam generation

GENERATION OF ELECTRON BEAMS IN MAGNETRON GUNS WITH SECONDARY EMISSION CATHODES OF A SMALL DIAMETER

This paper is concerned with investigations on electron beam generation in magnetron guns with cold secondary-emission metallic cathodes of a small diameter with a large aspect ratio. The parameters of electron beams are given as a function of electric and magnetic field values using different methods of voltage pulse formation for secondary-electron multiplication and beam generation

Analysis of chemical interactions during filling a cesium vapor cell for a quantum magnetometer

The results of the development and research of the technological process for manufacturing spherical vapor cells are presented. Such cells are used in quantum devices, such as magnetometers, gyroscopes, and atomic clocks. Their work is based on optical pumping and detection of the state of alkali metal vapors, in particular cesium. To increase the lifetime of cesium spin polarization in the vapor cell, it is filled with a buffer inert gas. The quality of cell manufacturing directly affects such device characteristics as the width of resonance lines and the achievable signal-to-noise ratio. The proposed cell manufacturing technology simplifies the technological process, eliminates the use of specialized equipment, and increases the reproducibility of results associated with chemical reactions of an alkali metal with foreign impurities in a buffer gas. This is achieved by detecting the formed compounds and excluding them from the composition of the gaseous environment of the cells through the selection of a reasonable sequence of technological operations in the cell manufacturing cycle. The use of traditional methods of X-ray diffraction is associated with the need to depressurize the vapor cell with cesium which leads to the inevitable reaction of cesium with components of the air environment. The work proposes a two-stage analytical assessment of the composition of the gas mixture. At the first stage, the thermodynamic resolution of all possible reactions in the cesium-nitrogen-impurity oxygen system is determined. At the second stage, the color spectrum of the spectra of experimentally obtained reaction products is compared with the color of the products of thermodynamically allowed interactions. Thermodynamic analysis based on a two-stage approach made it possible to identify the formation of cesium suboxides in a vapor cell when it was heated in the temperature range of 273–700 K. To exclude them from the composition of the vapor cell, a sequence of operations was proposed. It involves the formation of an ampoule using the glass blowing method which has a technological cylindrical part and a spherical cell connected to it by a constriction. High purity cesium encapsulated in a glass shell is placed into the technological part of the ampoule, after which the ampoule is evacuated. After opening the capsule with cesium, thermal distillation of pure cesium into a spherical zone takes place. The technological process is completed by filling the cell with buffer gas, after which it is sealed off. The absence of heating during filling a vapor cell with nitrogen significantly simplifies the technological process and minimizes the amount of foreign impurities in the form of cesium suboxides in the gas mixture

On the vibron dressing in the α\alpha--helicoidal macromolecular chains

We present a study of the physical properties of the vibrational excitation in $\alpha$--helicoidal macromolecular chains, caused by the interaction with acoustical and optical phonon modes. The influence of the temperature and the basic system parameters on the vibron dressing has been analyzed by employing the simple mean--field approach based on the variational extension of the Lang--Firsov unitary transformation. Applied approach predicts a region in system parameter space where one takes place an abrupt transition from partially dressed (light and mobile) to fully dressed (immobile) vibron states. We found that the boundary of this region depends on system temperature and type of bond among structural elements in the macromolecular chain.Comment: 22 pages, 12 figures, title changed, the interaction with optical phonon modes jointly with acoustical ones added, consideration significantly enlarged, references added, the paper develops the results of arxiv:1210.3918, accepted for publication in Chinese Physics

Безопасность и эффективность 23-валентной полисахаридной пневмококковой вакцины у больных системной красной волчанкой

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy > 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs <1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated <1 year before immunization. Further long-term prospective studies in large patient cohorts are required.Цель исследования – изучение безопасности и эффективности 23-валентной полисахаридной пневмококковой вакцины (ППВ-23) у больных системной красной волчанкой (СКВ).Пациенты и методы. В исследование включено 75 пациентов с достоверным диагнозом СКВ в возрасте 19–68 лет, 10 (13%) из них имели высокую активность СКВ, 18 (24%) – среднюю, 42 (56%) – низкую, у 5 (7%) – выявлена ремиссия заболевания. ППВ-23 вводили подкожно в разовой дозе 0,5 мл. У 60 пациентов срок наблюдения составлял ≥12 мес, у 15 – от 2 до 6 мес. Больных обследовали до и через 1, 3 и 12 мес после иммунизации.Результаты и обсуждение. У 38 (50,7%) пациентов отмечались стандартные местные вакцинальные реакции легкой и средней степени выраженности, у 1 (1,3%) – общая реакция легкой степени выраженности, у 2 (2,7%) – легкая диарея в течение 1 сут, у 1 (1,3%) – гиперергическая реакция по типу феномена Артюса, симптомы которой были купированы за 7 дней. На протяжении 12 мес наблюдения не выявлено ни одного случая обострения СКВ, достоверно связанного с вакцинацией, а также новых аутоиммунных феноменов. Через 1 год наблюдения число ответивших на вакцинацию составило 58%, не ответивших – 42%. Длительность и активность заболевания, возраст старше 50 лет, прием глюкокортикоидов в дозе >10 мг/сут значимо не влияли на вакцинальный ответ. Отмечено снижение иммунного ответа на фоне терапии генно-инженерными биологическими препаратами (ГИБП) по сравнению с отсутствием данного лечения (43 и 68% случаев соответственно), р=0,058. Различий на фоне применения ритуксимаба и белимумаба не установлено. Обнаружена тенденция к преобладанию ответивших на вакцинацию среди больных, получавших ГИБП <1 года до иммунизации, а также среди пациентов, которым эта терапия была инициирована после введения ППВ-23. Наблюдалась положительная динамика в виде уменьшения эпизодов пневмоний, острого и обострения хронического бронхита, синуситов.Заключение. Показаны достаточная иммуногенность, хорошая переносимость и клиническая эффективность ППВ-23 у больных СКВ, в том числе получавших комбинированную иммуносупрессивную терапию. Применение ГИБП уменьшает число пациентов с вакцинальным ответом. Если иммунизацию проводить до начала терапии ГИБП или на фоне такого лечения длительностью <1 года, то число ответивших на вакцинацию возрастает. Необходимы дальнейшие длительные проспективные исследования на больших выборках пациентов

Факторы риска развития и проявления острого холангита у больных с доброкачественной обструкцией внепеченочных желчных путей

Цель. Определение факторов, способствующих развитию острого холангита (ОХ) или являющихся его признаками при доброкачественной обструкции внепеченочных желчных путей (ДОВЖП). Материалы и методы. Ретроспективно проанализированы 144 наблюдения ДОВЖП, ОХ отмечен в 17 наблюдениях. Проведено сравнение встречаемости различных факторов и признаков у больных с ОХ и без ОХ. Результаты. Различия выявлены (p 0,05) между следующими показателями: пол, возраст, индекс массы тела, наличие абдоминального болевого синдрома, холецистэктомия в анамнезе, объем ЖП, причина обструкции, расширение гепатикохоледоха, эндоскопическая папиллосфинктеротомия в анамнезе, наличие околососочкового дивертикула и острого билиарного панкреатита. Выводы. Факторы риска развития ОХ: уровень общего билирубина 70 мкмоль/л и выше, утолщение стенки ЖП до 4 мм и более, отключенный ЖП, фиксированный камень БСДПК, размер БСДПК 15 мм и более. Проявления ОХ: гипертермия, наличие триады Шарко, лейкоцитоз 9 × 109 в 1 л и выше, увеличение содержания палочкоядерных нейтрофилов до 7% и выше, гиперамилаземия

On the vanishing electron-mass limit in plasma hydrodynamics in unbounded media

We consider the zero-electron-mass limit for the Navier-Stokes-Poisson system in unbounded spatial domains. Assuming smallness of the viscosity coefficient and ill-prepared initial data, we show that the asymptotic limit is represented by the incompressible Navier-Stokes system, with a Brinkman damping, in the case when viscosity is proportional to the electron-mass, and by the incompressible Euler system provided the viscosity is dominated by the electron mass. The proof is based on the RAGE theorem and dispersive estimates for acoustic waves, and on the concept of suitable weak solutions for the compressible Navier-Stokes system